Abstract
Schizophrenia is a chronic and debilitating neuropsychiatric disorder affecting approximately 1% of the world’s population. This disease is associated with considerable morbidity placing a major financial burden on society. Antipsychotics have been the mainstay of the pharmacological treatment of schizophrenia for decades. The traditional typical and atypical antipsychotics demonstrate clinical efficacy in treating positive symptoms, such as hallucinations and delusions, while are largely ineffective and may worsen negative symptoms, such as blunted affect and social withdrawal, as well as cognitive function. The inability to treat these latter symptoms may contribute to social function impairment associated with schizophrenia. The dysfunction of multiple neurotransmitter systems in schizophrenia suggests that drugs selectively targeting one neurotransmission pathway are unlikely to meet all the therapeutic needs of this heterogeneous disorder. Often, however, the unintentional engagement of multiple pharmacological targets or even the excessive engagement of intended pharmacological targets can lead to undesired consequences and poor tolerability. In this article, we will review marketed typical and atypical antipsychotics and new therapeutic agents targeting dopamine receptors and other neurotransmitters for the treatment of schizophrenia. Representative typical and atypical antipsychotic drugs and new investigational drug candidates will be systematically reviewed and compared by reviewing structure-activity relationships, pharmacokinetic properties, drug metabolism and safety, pharmacological properties, preclinical data in animal models, clinical outcomes and associated side effects.
Keywords: Antipsychotic, Aripiprazole, Clozapine, Dopamine, Haloperidol, ITI-007, Risperidone, Schizophrenia.
Current Topics in Medicinal Chemistry
Title:Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future
Volume: 16 Issue: 29
Author(s): Peng Li, Gretchen L. Snyder and Kimberly E. Vanover
Affiliation:
Keywords: Antipsychotic, Aripiprazole, Clozapine, Dopamine, Haloperidol, ITI-007, Risperidone, Schizophrenia.
Abstract: Schizophrenia is a chronic and debilitating neuropsychiatric disorder affecting approximately 1% of the world’s population. This disease is associated with considerable morbidity placing a major financial burden on society. Antipsychotics have been the mainstay of the pharmacological treatment of schizophrenia for decades. The traditional typical and atypical antipsychotics demonstrate clinical efficacy in treating positive symptoms, such as hallucinations and delusions, while are largely ineffective and may worsen negative symptoms, such as blunted affect and social withdrawal, as well as cognitive function. The inability to treat these latter symptoms may contribute to social function impairment associated with schizophrenia. The dysfunction of multiple neurotransmitter systems in schizophrenia suggests that drugs selectively targeting one neurotransmission pathway are unlikely to meet all the therapeutic needs of this heterogeneous disorder. Often, however, the unintentional engagement of multiple pharmacological targets or even the excessive engagement of intended pharmacological targets can lead to undesired consequences and poor tolerability. In this article, we will review marketed typical and atypical antipsychotics and new therapeutic agents targeting dopamine receptors and other neurotransmitters for the treatment of schizophrenia. Representative typical and atypical antipsychotic drugs and new investigational drug candidates will be systematically reviewed and compared by reviewing structure-activity relationships, pharmacokinetic properties, drug metabolism and safety, pharmacological properties, preclinical data in animal models, clinical outcomes and associated side effects.
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Cite this article as:
Li Peng, Snyder L. Gretchen and Vanover E. Kimberly, Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future, Current Topics in Medicinal Chemistry 2016; 16 (29) . https://dx.doi.org/10.2174/1568026616666160608084834
DOI https://dx.doi.org/10.2174/1568026616666160608084834 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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